Mean improvement in the glomerular filtration rate (GFR) was 6.1 ml/min/year among patients who achieved a hematologic CR or a VGPR at 6 months, compared to a mean GFR loss of 6.5 ml/min/year among those who achieved a partial response or no response to first-line chemotherapy.

In a cohort of 53 patients with biopsy-proven light chain deposition disease (LCDD), deep clonal responses to chemotherapy significantly improved renal outcomes in patients with LCDD, even when they had advanced chronic kidney disease (CKD).

"The prolonged follow up of this large cohort of patients highlights systematically for the first time in LCDD the relationship between the response to chemotherapy of the underlying hematologic disease and renal outcome," lead author Rabya Sayed, MBBS, National Amyloidosis Centre, Royal Free Campus, London, U.K. and colleagues wrote in Blood.

"[These] data clearly indicate that one should strive to achieve a hematologic CR (complete response) when treating patients with LCDD, even in the context of pre-existing stage 4 CKD (chronic kidney disease)."

Mean improvement in the glomerular filtration rate (GFR) was 6.1 ml/min/year from a baseline of 26 ml/min/year among 21 patients who achieved a complete hematologic response or a very good partial hematologic response at 6 months, compared to a mean GFR loss of 6.5 ml/min/year among those who achieved either a partial response or no response to first-line chemotherapy (P<0.009).

Only three out of 21 patients who achieved a complete or very good partial response to first-line chemotherapy required renal replacement therapy during follow-up compared to seven out of 11 patients who achieved either a partial response or who did not respond to chemotherapy.

Sixteen patients received an ASCT, four of whom were dialysis-dependent prior to transplantation.

The median GFR prior to undergoing ASCT among patients not requiring dialysis was 24 ml/min (range 11 to 51 ml/min) which increased among surviving patients to 38 ml/min at the end of follow-up.

Of the 15 patients who survived the ASCT, 13 achieved a hematologic complete response and two achieved a partial response and only two patients required further chemotherapy for hematologic relapse administered approximately 5 years after undergoing ASCT.

Seven patients from the cohort underwent renal transplantation and in three of these patients, the transplant failed, two from recurrence from LCDD.

The four remaining patients had GFRs of approximately 45 or more ml/min after renal transplantation and among those whose underlying clonal disorder was in sustained remission, there was no recurrence of LCDD up to 9.7 years later.

The median estimated survival from diagnosis for the whole cohort was 14 years.

Fifty-one of the 53 patients enrolled in the cohort were diagnosed with LCDD on renal histology, the other two being diagnosed on liver biopsy.

Median age at diagnosis was 56 years and at least 90% of the cohort were hypertensive and had hematuria at the time of diagnosis.

Among 43 patients who were not receiving renal replacement therapy at the time of diagnosis, the mean rate of GFR decline was 3.7 ml/min/year prior to dialysis initiation or death.

Dialysis was initiated in 23 additional patients during follow-up with a median survival in renal function from baseline of 5.4 years.

"Unsurprisingly, CKD stage at diagnosis had a significant impact on renal survival," investigators note, "with those who had CKD stage 2 or 3 at diagnosis remaining dialysis independent for a median of 9 years compared to only 2.7 years among those with CKD stage 4 or 5 at diagnosis (P=0.004)."

During the course of their disease, 62% of patients overall required dialysis and median patient survival from the time dialysis was initiated was 5.2 years.

"Rate of native GFR loss among those who did not achieve either a complete or a very good partial hematologic response with chemotherapy was 6.5 ml/min/year, higher than that reported for CKD generally where the average decline in GFR is between 0.5 and 2.5 ml/min/year," Sayed and colleagues observed.

"But this is not surprising, since these patients were continuing to deposit light chain in their kidneys."

The authors added that patients treated with chemotherapy while their GFR was > 30 ml/min had a substantially better renal survival at a median of about 9 years than patients who started chemotherapy having already reached stage 4 CKD.

The data also clearly indicate that ASCT can be successful, even when patients have a very low GFR (at a median of 24 ml/min in this cohort) with little apparent risk of precipitating an acute renal decline.

In contrast, the data also clearly show that renal transplants fail rapidly from recurrence of LCDD when patients do not achieve a good hematologic response.

"Patient survival as well as tolerance of high dose chemotherapy appears to be substantially better in LCDD than in systemic AL amyloidosis," Sayed and colleagues concluded.

"LCDD should be aggressively treated with chemotherapy since achieving a hematologic CR or VGPR prolongs renal survival even if advanced renal impairment has supervened."

Asked by MedPage Today to comment on the findings, Nelson Leung, MD, Mayo Clinic Rochester, Minnesota, felt that the study was important because it is one of the first studies to have assessed the response rate in this disease with the use of novel agents.

Novel agents used in multiple myeloma include immunomodulatory drugs such as lenalidomide, pomalidomide, and carfilzomib as well as the proteasome inhibitors, Leung noted.

LCDD is now considered to be a monoclonal gammopathy of renal significance and its presentation is dominated by renal damage and failure.

"If you look at this study, only 11% of patients had clonal plasma cells so that means if you just use the most liberal definition for myeloma, only 11% of patients in this series met the criteria for myeloma," Leung said.

In other words, the great majority of patients described in this paper had monoclonal gammopathy of renal significance, he added.

"This is important because all of the data we have had before came from patients who had multiple myeloma because typically only patients with multiple myeloma are treated," Leung explained.

"But this study shows that treatment of patients with monoclonal gammopathy of renal significance is beneficial even though they do not have multiple myeloma."

As Leung pointed out in his review in Blood (published online Oct. 9, 2012), multiple myeloma is the most frequent monoclonal gammopathy to involve the kidney even though a growing number of kidney diseases associated with other monoclonal gammopathies are gradually being recognized.

In addition to ESRD, the persistence of monoclonal gammopathy is associated with high rates of recurrence after kidney transplantation, Leung confirmed and preservation and restoration of kidney function are now possible with successful treatment targeting the responsible clone.

Accessibility Statement

At MedPage Today, we are committed to ensuring that individuals with disabilities can access all of the content offered by MedPage Today through our website and other properties. If you are having trouble accessing www.medpagetoday.com, MedPageToday's mobile apps, please email legal@ziffdavis.com for assistance. Please put "ADA Inquiry" in the subject line of your email.